Current evidence indicates that the gastrointestinal hormones - secretin, chole-cystokinin (CCK) and gastrin - greatly influence the flow rate and composition of hepatic bile. Although there is evidence to suggest that these hormones act on the same receptor site in the stomach and interact to control gastric acid output, little information is available concerning the receptor mechanisms of these hormones in the liver and biliary ducts. The principal investigator has shown in preliminary studies that pentagastrin produces similar qualitative and quantitative increases in hydrogen ion output from the canine stomach as does gastrin; but it does not produce similar changes in bile flow and composition. Gastrin increases bile flow while pentagastrin does not alter the flow rate or composition of hepatic bile. Preliminary investigations have also demonstrated that pentagastrin-stimulated hydrogen ion output from the stomach is greatly inhibited by both CCK and secretin, while CCK and secretin-stimulated bile flow is not altered by pentagastrin. This work suggests that the hormonal receptor interactions in the liver are different from those in the stomach. The objective of the proposed research is to evaluate the structural nature of the hepatic hormonal receptor sites, influencing the output and composition of hepatic bile, by receptor bioassay and kinetic analysis. Utilizing these techniqus we will evaluate the effect of exogenous and endogenous gastrin on CCK and secretin choleresis, the effect of gastrin on caerulein choleresis and the effect of glucagon on secretin choleresis. We will simultaneously evaluate the ability of these agents to alter the bile salt composition of hepatic bile. The results of these studies may contribute significantly to our concepts of the hormonal interactions in the production of bile. The results may also lead to the demonstration of inhibitory and augmentatory bile salt-producing agents.